DESCRIPTION (the Applicant's Abstract): With increasing age, there is increased incidence and severity of infectious diseases, including pneumonia, meningitis and sepsis, as well as many non-infectious diseases including cancers, heart disease, Alzheimer' s disease and other dementias. The obligate intracellular bacterial parasite Chlamydia pneumoniae is an established pathogen for respiratory infection. Recent evidence from a number of laboratories suggests that C. pneumoniae may be a factor in the pathogenesis of a number of non-respiratory diseases including Alzheimer's disease and atherosclerosis. It has been repeatedly hypothesized that increased incidence of infectious and other diseases with age may be the result of age alterations in the immune system, particularly in cell mediated immune reactions. It is well established that T cell function, as measured in vivo by delayed type hypersensitivity reactions and in vitro as proliferative responses to antigenic or mitogenic stimulation, both decline with age. While infection with C. pneumoniae as well as other Chlamydial species induces production of antibodies, recent evidence suggests that cell mediated immune mechanisms play a key role in recovery from infection as well as immunopathology associated with Chlamydial infection. It has not been established whether old animals are able to clear infection by C. pneumoniae or remain chronically infected. It also remains unknown whether the immune response, particularly the cell-mediated immune response, to acute chlamydial infection is altered with age. Finally, the extent to which the cell-mediated immune response to Chlamydia, or lack thereof, contributes to the pathogenesis of diseases such as atherosclerosis or Alzheimer's disease is entirely speculative. We propose here to begin to address these issues in a mouse model. The working hypothesis is that the cellular immune response against C. pneumoniae declines with age. The Specific Aims of this project are: 1) To assess whether aging is associated with alterations in the clinical course of experimental intranasal infection of mice by C. pneumoniae; and 2) To assess whether there are age-associated changes in the immune response to C. pneumoniae. Specifically, we will examine proliferative responses, generation of cytotoxic T cells, and production of Th1 associated cytokines (IL-2 and IFN-g).